Multiple-dose升级安全的研究、药物动力学和生物活动的口服AMD070,选择性趋化因子受体CXCR4受体抑制剂,在人类主题。

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石头ND, Dunaway某人,Flexner C, C Tierney, Calandra GB,贝克尔年代,曹YJ,韦根IP,康利J, MacFarland RT,公园詹,Lalama C,斯奈德年代,Kallungal B, Klingman KL,亨德里克斯连续波

Multiple-dose升级安全的研究、药物动力学和生物活动的口服AMD070,选择性趋化因子受体CXCR4受体抑制剂,在人类主题。

Antimicrob代理Chemother。2007年7月,51 (7):2351 - 8。Epub 2007年4月23日。

PubMed ID

17452489 (在PubMed

]

文摘

AMD070是口服趋化因子受体CXCR4拮抗剂在体外对X4-tropic人类免疫缺陷病毒1型活动。三十禁食健康男性志愿者口服剂量的AMD070从一个50毫克剂量7 400毫克剂量给予每12 h (q12h)。九个学科获得200毫克剂量在空腹和餐前。受试者安全监测和药物动力学。AMD070耐受性良好,没有严重的不良事件。瞬态头痛(13科目)和神经认知(8科目)和胃肠道(7主题)症状最常见的投诉。七个受试者窦性心动过速,两个症状。AMD070血浆浓度峰值1到2 h后病人剂量。终端的半衰期估计范围从11.2到15.9 h组之一。剂量比例没有演示。 Less than 1% of the drug appeared unchanged in the urine. Food reduced the maximum concentration of drug in serum and the area under the concentration-time curve from 0 to 24 h by 70% and 56%, respectively (P < or = 0.01). A dose-dependent elevation of white blood cells (WBC) demonstrated a maximum twofold increase over baseline (95% confidence interval, 2.0- to 2.1-fold) in an E(max) model. In healthy volunteers, AMD070 was well tolerated and demonstrated mixed-order pharmacokinetics, and food reduced drug exposure. AMD070 induced a dose-related elevation of WBC which was attributed to CXCR4 blockade. Using leukocytosis as a surrogate marker for CXCR4 inhibition, this dose-response relationship suggests that the doses used in this study were active in vivo, though not maximal, throughout the dosing interval. Trough concentrations with the 400-mg dose q12h exceeded the antiviral in vitro 90% effective concentration of AMD070.

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